Devices that deliver drugs through skin for absorption into the body are known in the art. For example, U.S. Pat. No. 4,915,950 to Miranda et al, describes a transdermal drug delivery device including an absorbent source layer laminated to a pressure sensitive pharmaceutically acceptable contact adhesive. The source layer has an anchor adhesive layer laminated to its opposing side and a drug-impermeable backing layer applied to the anchor adhesive.
U.S. Pat. No. 4,817,594 to Juhasz, describes an integral anti-bacterial wound dressing containing the following five layers: the first layer of a permeable material; a layer of semipermeable material; a layer of electrically-conducted material in the form of an open mesh; a layer of charcoal fabric; and a non-adherent wound facing second layer of a permeable material.
U.S. Pat. No. 4,687,476 to Pailin, describes a continuous multi-layer strip used as a topical dressing, wherein the strip has a continuous layer of a first foil and on one side thereof a laminated material comprising a layer of skin adhesive protected with a release film.
U.S. Pat. No. 4,542,013 to Keith, describes a trinitroglycerol-containing substantially disaccharide-free polymeric diffusion matrix for transdermal systemic delivery of trinitroglycerol. The bandage may also include a facestock layer with skin adhesive, which comprises a foam, film-type, non-woven or vinyl tape with an acrylic, silicon or rubber adhesive.
U.S. Pat. No. 5,217,718 to Colley et al, describes a therapeutic system for the transdermal administration of dexmedetomidine that is a laminated composite of a backing layer, an optional anchor adhesive layer, a contact adhesive layer; and one or more additional layers. The composite also preferably contains an optional porous intermediate layer between the anchor and contact adhesive layer, wherein, when an anchor is included, it is typically an absorbent, non-woven fabric.
U.S. Pat. No. 5,298,258 to Akemi et al, describes an acrylic oily gel bioadhesive material comprising a substrate having on one surface thereof, a crosslinked gel layer.
U.S. Pat. No. 4,938,964 to Sakai et al, describes a formulation which may be applied using a conventional support. A cotton or non-woven fabric may be used for the support.
U.S. Pat. No. 4,904,475 describes a porous support structure for use in a device for delivering ionized drugs from an aqueous reservoir.
U.S. Pat. No. 5,411,740 describes the transdermal administration of oxybutynin and related compounds for the treatment of neurogenic bladder disease, among other things. (All of the aforementioned U.S. Patents are incorporated herein in their entirety by reference. )
In addition, Black "Transdermal Drug Delivery Systems", US Pharmacist, November 1982, pp 49-78, provides additional background information regarding commercially available transdermal drug delivery systems. A reasonably complete summary of the factors involved in percutaneous absorption of drugs may be found in Arita, et al, "Studies on Percutaneous Absorption of Drugs", Chem. Phar. BUll., Vol. 18, 1970, pp 1045-1049; Idson, "Percutaneous Absorption", J. Phar. Sci., Vol. 64, No. 6, pp 910-922; and Clooney, Advances in Biomedical Engineering, Part I, Chapter 6, "Drug Permeation Through Skin: Controlled Delivery For Topical or Systemic Therapy", Marcel Dekker, Inc., New York and Basel, 1980, pp 305-318.
Although the transdermal drug delivery route is rapidly becoming a preferred delivery route for a wide variety of drugs, transdermal delivery is not without its problems. In general, direct contact of an adhesive with a drug reservoir which contains an amphipathic molecule, eg, a non-ionic surfactant such as a permeation enhancer, eg, a monoglyceride, ie, glycerol monolaurate or glycerol monooleate, has a problem of blooming at the interface of the contact adhesive/drug reservoir. The occurrence of blooming is caused by the surfactant migrating to the relatively lower energy interface generated by laminating an adhesive to the reservoir. The interface then swells or blooms, causing delamination between the contact adhesive and drug reservoir.
Additionally, the use of a permeation enhancer in any transdermal drug delivery device necessarily complicates the design and development of the device. Permeation enhancers cause compatibility problems throughout the delivery system. Instead of having to characterize the properties of the reservoir compositions, adhesives, and release-controlling materials with respect to just the drug, these materials must now have the proper characteristics with respect to both the drug and the permeation enhancer. Typically, drugs and permeation enhancers have very different physical and chemical properties, and, in most cases, the properties of mixtures of the drug with the permeation enhancer is unknown. For example, permeation enhancers can cause, among other problems, cohesive failure of adhesive and can partition through other components in the system.